What alternative to Jardiance (empagliflozin) is appropriate for a patient with type 2 diabetes who has recurrent genital yeast infections?

Alternative SGLT2 Inhibitor for Recurrent Genital Yeast Infections

If recurrent genital yeast infections make Jardiance (empagliflozin) intolerable, switch to a GLP-1 receptor agonist such as semaglutide, dulaglutide, or liraglutide, which provide comparable cardiovascular and renal protection without increasing infection risk. 1

Why SGLT2 Inhibitors Cause Genital Infections

• All SGLT2 inhibitors—including empagliflozin (Jardiance), dapagliflozin (Farxiga), and canagliflozin (Invokana)—induce glucosuria by blocking renal glucose reabsorption, creating a glucose-rich environment in the genital area that promotes fungal overgrowth. 2

• Genital mycotic infections occur in approximately 6% of patients on any SGLT2 inhibitor versus 1% on placebo, with no clinically meaningful difference in infection rates between empagliflozin, dapagliflozin, or canagliflozin. 3, 4

• Switching from one SGLT2 inhibitor to another will not reduce infection risk because the mechanism—drug-induced glucosuria—is identical across the entire class. 3

Preferred Alternative: GLP-1 Receptor Agonists

GLP-1 receptor agonists deliver robust cardiovascular and renal protection equivalent to SGLT2 inhibitors without increasing genitourinary infection risk. 1

Specific Agent Selection

• Semaglutide (Ozempic, Wegovy, Rybelsus) reduces cardiovascular death, myocardial infarction, and stroke, and lowers new or worsening nephropathy by 36% (composite of persistent UACR >300 mg/g, doubling of serum creatinine, or end-stage renal disease). 1

• Dulaglutide (Trulicity) and liraglutide (Victoza) provide similar cardiovascular benefits and require no dose adjustment in chronic kidney disease. 1

• All three agents can be used when eGFR is >30 mL/min/1.73 m² without dose modification. 1

Clinical Decision Algorithm

Step 1: Confirm Recurrent Infections

• Define recurrence as ≥4 episodes of genital candidiasis per year despite standard antifungal therapy and proper hygiene counseling. 3

Step 2: Discontinue Jardiance

• Stop empagliflozin immediately if recurrent infections markedly impair quality of life or fail to respond to maintenance antifungal therapy. 3

Step 3: Initiate GLP-1 Receptor Agonist

• Start semaglutide 0.25 mg subcutaneously once weekly, titrating to 0.5 mg after 4 weeks and to 1 mg after another 4 weeks if tolerated. 1

• Alternatively, initiate dulaglutide 0.75 mg subcutaneously once weekly, with option to increase to 1.5 mg after 4 weeks. 1

• For patients preferring oral therapy, consider oral semaglutide (Rybelsus) 3 mg daily, titrating to 7 mg and then 14 mg at monthly intervals. 1

Step 4: Continue Metformin

• Maintain metformin if eGFR ≥30 mL/min/1.73 m²; reduce dose to ≤1000 mg/day if eGFR is 30–44 mL/min/1.73 m². 1

Step 5: Monitor Cardiovascular and Renal Outcomes

• GLP-1 receptor agonists provide cardiovascular death reduction and slow chronic kidney disease progression, preserving the benefits that would have been obtained from Jardiance. 1

Alternative Non-SGLT2 Options

DPP-4 Inhibitors

• Linagliptin (Tradjenta) requires no dose adjustment at any level of renal function and does not increase genitourinary infection risk. 1

• However, DPP-4 inhibitors lack the robust cardiovascular and renal protection demonstrated by SGLT2 inhibitors and GLP-1 receptor agonists. 1

Insulin

• Insulin remains fully effective regardless of renal function and can be used as the primary glucose-lowering agent when aggressive glycemic control is required. 1

• Insulin does not increase genital infection risk but lacks the cardiovascular and renal benefits of SGLT2 inhibitors and GLP-1 receptor agonists. 1

Management of Active Infections Before Switching

• Treat acute vulvovaginal candidiasis with oral fluconazole 150 mg as a single dose, which provides >90% clinical cure. 3

• For recurrent infections (≥4 episodes/year), use induction therapy with a 10–14-day course of topical azole or oral fluconazole, followed by maintenance therapy with weekly fluconazole 150 mg for 6 months. 3

• Despite successful maintenance, 40–50% of patients experience another episode within the following year, justifying permanent discontinuation of the SGLT2 inhibitor. 3

Common Pitfalls to Avoid

• Do not switch from empagliflozin to dapagliflozin or canagliflozin expecting lower infection rates; all SGLT2 inhibitors carry identical risk. 3, 4

• Do not continue SGLT2 inhibitor therapy with chronic suppressive antifungal treatment as a long-term strategy; this approach is not evidence-based and exposes patients to unnecessary antifungal toxicity. 3

• Do not delay switching to a GLP-1 receptor agonist in patients with established cardiovascular disease or chronic kidney disease; these patients derive the greatest absolute benefit from alternative cardioprotective therapy. 1

• Recognize Fournier's gangrene immediately—necrotizing fasciitis of the perineum requires urgent surgical debridement, broad-spectrum antibiotics, and permanent discontinuation of all SGLT2 inhibitors. 3